Stabilization of cellular constituents and biomolecules is critical for profiling both diseased and healthy tissue: therefore, considerable resources are spent on primary sample collection and storage. In addition, there have been tremendous advances in downstream molecular analytical systems. Nevertheless, the transition from a stabilized, frozen tissue sample to a homogenized solution ready for analysis is often overlooked as an area of potential improvement. The broad objective of this project is to design, build, and test a high-speed feedback loop system for the convergent acoustic energy systems developed by Covaris (e.g., El00). The current system uses pulsed megahertz ultrasound, which is deliberately limited to low duty cycles (e.g., 5%) to ensure that samples are not over processed. The specific aims of this Phase One application are to develop an acoustic-based, high-speed feedback loop module that will enable the Covaris sample preparation apparatus to homogenize solid tumor tissue specimens faster. The control system will monitor cavitation activity for each pulse of ultrasound and the cavitation signal will be used to control the next treatment pulse. In addition to reducing preparation time, a faster homogenization process is also expected to increase the recovery of biomolecules from tissue samples. The feedback-controlled process will result in more consistent sample preparation that should produce higher quality and reproducible samples for subsequent analysis. Improvements in molecular profiling may enable a new generation of biomarkers to be developed for screening, monitoring, and surveillance of cancer. Long-term objectives are to develop tools for basic, preclinical, and clinical research for improved molecular analysis. The processes that may be developed would be amenable for high-throughput sample preparation.